The efficient stereo- and enantioselective synthesis of complex arrays of acyclic stereocenters constitutes one of the most intriguing challenges in modern synthetic organic chemistry. The multitude of such acyclic arrays in macrolides, polyether antibiotics, complex carbohydrates and numerous other classes of biologically active natural products has provided considerable stimulus for the development of synthetic methodology that is practical, efficient, and applicable to a wide range of problems. The major objectives of this research program continue to be (1) the development of a family of highly enantioselective chiral allyl- and crotylboronates and (2) the application of this technology in the synthesis of biologically active, propionate-derived natural products. The tartrate ester modified allylboronates 1-3 developed in our laboratory function beautifully in matched double asymmetric reactions but often give less satisfactory results in mismatched double asymmetric reactions. Consequently, additional effort will be devoted to the development of improved, second generation reagents 63 and 68-70. Our observation that the % e.e. of the allylborations of unsaturated aldehydes is significantly enhanced by using metal carbonyl complexes as substrate surrogates will be applied in enantioselective syntheses of carbocyclin and of a key rutamycin B intermediate (124). Syntheses of streptovaricin D and bafilomycin A1 initiated in the previous grant period will be completed, and syntheses of zincophorin and rutamycin B will be initiated in the later years of this grant. Methods for construction the unusual quinone methide unit of streptovaricin D must be developed. A stereochemical study of the reactions of gamma-methoxyallylchromium and chiral aldehydes will be completed in connection with the bafilomycin synthesis, and additional studies into the factors that control the stereochemistry of the bafilomycin aldol coupling reaction (55 and 28) will be performed. Aldol reactions for fragment assembly steps in the rutamycin synthesis also will be examined. These studies provide the opportunity to define the stereochemical preferences of the Lewis acid catalyzed aldol reactions of enol silanes prepared from chiral alpha-methyl ketones, the results of which will be of considerable significance particularly if substantial selectivity is observed.